Abstract

^ Brains On-Line, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands

* Department of Electrophysiology, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark

Received 14 August 2006; received in revised form 18 December 2006; accepted 3 January 2007; Available online 19 January 2007.

Gaboxadol has been suggested to be a selective extrasynaptic GABA A receptor agonist. However, there is little information on Gaboxadolconcentrations in the central nervous system (CNS) at therapeutically relevant doses. In order to investigate this, rats were injected subcutaneously with Gaboxadol and plasma and CNS concentrations were determined using the dynamic-no-net-flux and ultraslow microdialysis methods. Results using the 2 methods were similar and showed that Gaboxadol rapidly entered the brain and that peak CNS concentrations after 2.5, 5 and 10 mg/kg were in the range of 0.7 to 3 μM. Furthermore, a very short half-life (28 min) in both plasma and CNS was observed. It is concluded thatconcentrations of Gaboxadol in the CNS are in a range, which are likely to activate only extrasynaptic (nongamma subunit containing) GABA A receptors.

© 2007 Elsevier B.V. All rights reserved.

Index Terms: Gaboxadol; Microdialysis; GABA; In vivo; (Rat)